[gmx-users] Umbrella sampling for protein-drug system
Justin A. Lemkul
jalemkul at vt.edu
Sun Feb 20 19:04:25 CET 2011
Aldo Segura wrote:
> Dear gmx-users,
> I have following the umbrella sampling tutorial at
> I’m trying to use it for a drug-protein system. In the tutorial the
> group A moves away to group B. I would like to pull the drug to the
> protein binding-site (i.e., drug move closer to protein). How can I do
> that? Should I modified the md_pull.mdp file (from the tutorial)
> changing the value from pull_rate1 (0.01) to a negative value (i.e.
> -0.01)? or using pull_geometry = position and related code instead
> pull_geometry = distance?
You may have to make several changes. Changing the sign of pull_rate1 will
indeed decrease the COM distance rather than increase it. Most of the
pull_geometry values could be useful here, but changing the method may require
other changes to the pulling settings. Refer to the manual.
Note that hitting a moving target is substantially harder than inducing a simple
dissociation of a protein complex, as the tutorial does. You may be able to
carefully set a pull_group0 and an appropriate vector along which to pull your
ligand, but if the protein diffuses or rotates even a small amount (which it
will), you will likely crash your ligand into some non-target region. A variety
of restraints could be used to prevent this from happening, but you may have a
hard time ensuring that the restraints do not adversely affect the dynamics of
the binding process.
Probably a more effective approach is to start from a docked complex and pull
the ligand out. If you're only looking for a PMF, you can accomplish the same
results by doing so, and it is substantially easier.
> Thanks in advance,
> Aldo Segura-Cabrera
> Laboratorio de Bioinformática
> Centro de Biotecnología Genómica
> Instituto Politécnico Nacional
> Blvd. Del Maestro esquina Elías Piña, 88710
> Reynosa, Tamaulipas, México.
> (899)9243627 ext. 87747
> e-mail: asegurac at ipn.mx <mailto:asegurac at ipn.mx>; aldosegura at gmail.com
> <mailto:aldosegura at gmail.com>
Justin A. Lemkul
ICTAS Doctoral Scholar
Department of Biochemistry
jalemkul[at]vt.edu | (540) 231-9080
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